The growth of the older adult population, increased prevalence of many disabling conditions, and high costs of institutional care are placing heavy demands on family members to provide informal caregiving services to adults with disabilities. Many previous studies have characterized caregiving as a chronic stress experience associated with poorer health and biomarker indicators of inflammation and compromised immunity. However, the vast majority of existing studies have been based on convenience samples and cross-sectional comparisons, and relatively few studies of caregiving have used population-based samples or prospectively examined transitions into the caregiving role within individual participants. The proposed study will identify individuals who have transitioned from a non-caregiving role into a family caregiving relationship while participating in a large, prospective, epidemiological study. The REasons for Geographic And Racial Differences in Stroke (REGARDS) project is an ongoing epidemiological study with over 17,800 active middle-aged and older participants as of May 31, 2015. Pilot data suggest that over 1,200 of these participants have transitioned from a non-caregiving role at REGARDS baseline (8-12 years ago) into an informal family caregiving role at the present time. Serum samples were collected and stored from an initial REGARDS in-home assessment, and follow-up serum samples are now being collected as part of a 2nd REGARDS in-home assessment. We propose to identify and enroll 300 participants from REGARDS who have transitioned into a family caregiving role between these two REGARDS in-home assessments and who continue to be caregivers at the 2nd in- home assessment. We will compare these caregivers to 300 individually-matched non-caregivers. A multi- step matching and covariate-adjustment procedure will be used to control for many potential confounding variables including demographics, socioeconomic status, prior health status, and family relationship factors. Changes over a 10-year period on a set of inflammatory biomarkers (e.g., CRP, IL-6, d-dimer, TNF-R1), health biomarkers (e.g., lipids, HgA1c), and self-reported health outcome measures (e.g., health-related quality of life, depressive symptoms, health behaviors) will be compared between incident caregivers and matched non- caregivers. Important subgroup comparisons will include a focus on the 30% of caregivers who are expected to be caring for a family member with Alzheimer's disease or another form of dementia. The proposed Caregiving Transitions Project will be the first population-based study ever conducted on the impact of transitioning into a caregiving role on serum-based biomarkers and other important health-related outcomes. Critical new knowledge will be provided for better understanding the health impact of informal caregiving, which will be an even more critical healthcare resource in the coming years.